title: Ang II Upregulation of the T-lymphocyte renin-angiotensin system is amplified by low-grade inflammation in human hypertension.
abstract: BACKGROUND
  Low-grade inflammation facilitates the development of essential hypertension and target organ damage (TOD). Recently, human T-lymphocytes were shown to be endowed with a functional active renin-angiotensin system (RAS). We investigated whether in hypertensive patients a selective angiotensin (Ang) II-driven upregulation of T-cell RAS occurs and whether it is differently modulated in presence of low-grade inflammation.
  
  
  METHODS
  T-lymphocytes were obtained from 21 hypertensives (I-II World Health Organization class; 16 males, 5 females; 56 ± 11 years). Low-grade inflammation was defined for high sensitive C-reactive protein (hsCRP) > 2 mg/l. Ten healthy subjects formed the age- and sex-matched control group. After T-lymphocytes isolation, mRNAs for angiotensin-converting enzyme (ACE) and angiotensin type 1 receptor (AT1-R) were quantified by reverse-transcriptase PCR with or without 0.1 pmol/l Ang II in addition to T-cells cultures. Cell pellet and supernatant ACE activity and Ang II content were measured. Cardiac and renal TOD-indexes were evaluated.
  
  
  RESULTS
  Both in controls and hypertensives, Ang II-stimulation significantly increased ACE and AT1-R mRNA levels (P < 0.05). In patients, the increase was earlier and higher than controls, with the highest values in hypertensives with > 2 mg/l hsCRP. Peak Ang II-induced ACE and AT1-R mRNA levels were positively related to hsCRP, systolic blood pressure and body mass index (BMI) at the univariate analyses. The stepwise regression analyses selected hsCRP (r = 0.47) and left ventricular mass index (LVMI) (r = 0.50) as the variables independently related to peak ace-gene expression, while BMI resulted independently related to peak AT1-R gene expression (P < 0.001).
  
  
  CONCLUSIONS
  In hypertension, an Ang II-driven activation of T-cell RAS, further amplified by low-grade inflammation, does occur and is associated to worse TOD. New therapeutic approaches aimed at this specific target might be proposed to control hypertension and hypertensive damage.
authors.affiliation: Department of Medical and Surgical Critical Care, University of Florence, Italy.
authors.forename: Mirella
authors.initials: M
authors.lastname: Coppo
authors.forename: Manuela
authors.initials: M
authors.lastname: Bandinelli
authors.forename: Andrea
authors.initials: A
authors.lastname: Berni
authors.forename: Sara
authors.initials: S
authors.lastname: Galastri
authors.forename: Rosanna
authors.initials: R
authors.lastname: Abbate
authors.forename: Loredana
authors.initials: L
authors.lastname: Poggesi
authors.forename: Fabio
authors.initials: F
authors.lastname: Marra
authors.forename: Gian Franco
authors.initials: GF
authors.lastname: Gensini
authors.forename: Maria
authors.initials: M
authors.lastname: Boddi
mesh_terms: D000368:Aged; D000804:Angiotensin II / Q000494:pharmacology*; D002097:C-Reactive Protein / Q000378:metabolism; D005260:Female; D006801:Humans; D006973:Hypertension / Q000503:physiopathology*; D007249:Inflammation / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000235:genetics; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics; D012084:Renin-Angiotensin System / Q000187:drug effects*; D013601:T-Lymphocytes / Q000187:drug effects / Q000502:physiology*; D015854:Up-Regulation
chemical_list: D044140:Receptor, Angiotensin, Type 1; D000804:Angiotensin II; D002097:C-Reactive Protein; D007703:Peptidyl-Dipeptidase A